Optic neuropathy or, often called, optic atrophy describes the loss of some or most of the fibers of the optic nerve. The optic nerve contains axons of nerve ceils that emerge from the retina, leave the eye at the optic disc and proceed to the visual cortex where input from the eye is processed into vision. There are 1.2 million optic nerve fibers that derive from the retinal ganglion cells of the inner retina, Damage or death of the nerve cells results in loss of vision.
Optic neuropathy may be caused by ischemic optic neuropathies, optic neuritis, compressible optic neuropathies, Infiltrative optic neuropathies, traumatic optic neuropathies, mitochondrial optic neuropathies, nutritional optic neuropathies, toxic optic neuropathies and hereditary optic neuropathies. All of these different optic neuropathies are caused by various diseased states of the eye. For example, ischemic optic neuropathy is caused by insufficient blood flowing to the optic nerve, while compressive optic neuropathy Is caused by tumors, infections and Inflammatory processes that can cause lesions within the eye orbit or optic canal. Trauma to the head when exposed to direct or indirect injury can cause traumatic optic neuropathy such as blunt trauma to the forehead during an automobile accident, which can transgress the force without transgressing tissue planes.
Hereditary optic neuropathies include Leber's hereditay optic neuropathy, congenial optic atrophy and autosomal dominant optic atrophy, type Kjer, the latter of which is sometimes known as Kjer's syndrome.
Leber's Hereditary optic neuropathy otherwise known as LHON is a mitochondrially inherited degeneration of the retinal ganglion cells and their axons leading to acute or subacute loss of central vision, LHON is only transmitted through the mother and Is due to mutations in the mitochondrial genome at nucleotide positions 11778 (G->A), 3480 (G->A) and 14484 (T->C), Depending on the mutation, the degree of visual improvement does vary. For example, the 14484 mutation has a 37% to 71% chance of visual improvement, whereas the 11778 and the 3460 mutations have only a 4% chance of improvement (Stone et at, J. Neuro-opthalamol 12:10-4 (1992) Oostra et al, J. Med Genet 31:280-286 (1994)),
Leber's disease is characterized by bilateral painless, subacute visual failure that develops generally in the male population during young adult life. Affected individuals are usually asymptomatic until blurring is developed in the central visual field in one eye. The other eye is affected two to three months later. Visual acuity is severely reduced to counting fingers or worse, in the majority of cases and visual field testing shows an enlarged dense central or centrocecal scotoma.
Directed therapies for mitochondrial disorders are very limited. There are general therapies involving vitamins and cofactors, folic acid, vitamin B12, thiamine, riboflavin, L-carnitine, L-arginine and creatine; electron acceptors (vitamin C and menadiol; free radical scavengers CoQ10, idebenone, alpha-lipoic acid, minocycline, cyclosporine A, glutathione and vitamin E; and inhibitors of toxic metabolites such as dichloroacetate. All of these therapies are useful, but do not aid to ameliorate or maintain vision,
U.S. Patent application Serial No. 2010/0273894 A1 describes methods of treating Leber's hereditary optic neuropathy and dominant optic atrophy with tocotrienol quinones in order to alleviate the systems of the disease. Tocotrienols, as well as tocopherols are parent cozeners in the same vitamin E family and act as phenolic antioxidants. The compounds can be administered in a solid dosage form such as in tablets or in a liquid dosage form such as in solutions. The visual acuity is improved from below 20/400 to about 20/100.
Autosomal dominant optic atrophy or Kjer's syndrome is the most common type of hereditary optic neuropathies that affects optic nerves, causing reduced visual acuity and blindness. This syndrome begins in childhood and is due to mitochondrial dysfunction mediating the death of optic nerve fibers. Visual acuity is generally reduced in both eyes and severe visual loss occurs in 15% of the patients. Some patients have decreased visual acuity with age. Also patients have a generalized dyschromatopsia with blue-yellow and red-green defects. Visual fields in patient's with Kjers syndrome show central, paracentral or cecocentral scotomas.
Congenital optic atrophy is also a hereditary disease that causes degeneration or destruction of the optic nerve. The milder form of congenital optic atrophy is autosomal dominant and has a gradual onset of vision deterioration in childhood but little progression thereafter. The more severe form is autosomal recessive and is present at birth or within two years. This form is accompanied by nystagmus (involuntary eye movement). Congenital optic atrophy may also be referred to as optic nerve head pallor since a pale appearance of the optic nerve head can be seen at the back of the eye. The symptoms of this eye disease are a change in the optic disc and a decrease in visual function.
There is no known treatment for any optic neuropathy to date that is effective and aids to maintain or ameliorate visual acuity or visual field.
Thus, there is a need in the art to have an improved compositions to treat optic neuropathy and more especially, optic neuropathy caused by ischemic optic neuropathy, optic neuritis, compressible optic neuropathy, infiltrative optic neuropathy, traumatic optic neuropathy, mitochondrial optic neuropathies, nutritional optic neuropathies, toxic optic neuropathies and hereditary optic neuropathies such as Leber's, autosomal dominant optic atrophy, Kjer's disease, congenial optic atropy and inclusion of the central artery in the eye.
The present invention fulfills this need and provides ophthalmic compositions that are ophthalmic neuroprotectors to maintain or enhance visual acuity and visual field.
These and other objects are achieved by the present invention as evidenced by the summary of the invention, description of the preferred embodiments and the claims.